TABLE 4.

Approved drugs associated with both endocytosis and cytokine signaling. The drugs approved by the FDA or EMA are indicated with their reported pKd values for AAK1, BMP2K and GAK, and the targets in the cytokine signaling module (Figure 5) which they are reported to inhibit are listed. The highest pChembl value is that reported for the first listed target (i.e. for baricitinib the pChembl value is for JAK2). The drugs are listed in order of affinity for AAK1.

	Drug	AAK1	GAK	BMP2K	Cell based/Cell free	Cmax free (nM)	Cytokine signaling targets	Highest pChembl
		pKd	pKd	pKd
1	SUNITINIB	7.96	7.7	8.26	1–5	8	[LCK, MAP2K2, JAK2, TYK2, JAK1, PTK2B]	6.6
2	BARICITINIB	7.88	5.33	7.4	2–5	68	[JAK2, JAK1, JAK3, TYK2]	9.1
3	FEDRATINIB	7.46	7.33	7.51	30–100	170	[JAK2, LCK, TYK2, JAK1, JAK3, BTK, PTK2B]	9.0
4	MIDOSTAURIN	6.38	<4.48	6.6	1	<17	[LCK, JAK2, TYK2, SYK, JAK1, JAK3, PTK2B]	6.6
5	RUXOLITINIB	5.45	<4.48	6.68	7	45	[JAK2, JAK1, TYK2, JAK3]	10.4
6	BOSUTINIB	5.32	7.38	6.46	25	18	[MAP2K2, LCK, EPHA2, SYK, BTK, PTK2B]	8.0
7	PALBOCICLIB	5.38	<4.48	—	23	35	[JAK3]	7.2
8	ERLOTINIB	<4.48	6.29	5.51		180	[LCK, JAK3]	6.6
9	DASATINIB	<4.48	6.8	—		7	[LCK]	9.7
10	DACOMITINIB	<4.48	6.77	—		4	[BTK, LCK, EPHA2, TYK2, JAK3, SYK]	6.2
11	AFATINIB	<4.48	5.75	—		8	[LCK]	7.0
12	FOSTAMATINIB	<4.48	<4.48	—		15	[SYK]	7.8
13	PAZOPANIB	<4.48	<4.48	—		<1,000	[LCK]	6.3
14	TRAMETINIB	<4.48	<4.48	—		1	[MAP2K2]	8.8
15	GEFITINIB	<4.48	6.02	—		19	[LCK]	6.4
16	ALPELISIB	<4.48	5.3	—		560	[PIK3CG]	6.6